Existing polymerization methods fall into one of two basic types; (1) Addition or Chain Growth Polymerization; and (2) Condensation or Step-Growth Polymerization.
Chain growth polymerizations most commonly utilize monomers possessing reactive carbon-carbon double bonds, although other species, such as cyclic ethers, e.g., ethylene and propylene oxide and aldehydes, e.g., formaldehyde, can be polymerized in this way. These chain-growth polymerizations are characterized by the fact that the free radical, ionic or metal complex intermediates involved in the process are transient and can not be isolated. A generalized example for a simple free radical initiated vinyl polymerization is shown below: ##STR1##
Step-growth polymerizations involve reactions which occur between molecules containing multiple reactive groups which can react with each other. An example of this is the well-known reaction of a glycol and a dibasic aromatic acid to give a polyester.
It can be readily seen that the use of multiple reactive monomers posessing groups with similar or equivalent reactivities with this method produces a mixture of individual polymer species having random arrangements of monomeric sequences and only statistical control of the resulting stoichiometric make-up.
While many different variations of these two classes of polymerization reaction schemes exist, e.g. initiation may be cationic, radical, anionic, sequential aldol, ring-opening or displacement, and many different reactive species may be employed, e.g. electron deficient alkenes, epoxides, polyamines, hydroxyesters, etc., all of these variations possess a common limiting feature--they all rely on a statistical or average stoichiometric control of the final polymeric product. This is achieved through the careful selection and control of the reaction conditions, such a concentration of monomers, agitation conditions, catalyst level, time/temperature cycles, etc. These existing polymerization methods do not have any ability to control the exact constitution or length of any specific individual polymer chain. The properties of the polymers produced via these processes are, in fact, a statistical average of the properties of a complex mixture of subtly differing individual polymer species having a range of molecular weights and containing differing combinations and sequences of monomers along the chains. Even in the simplest example of a step growth polymerization involving only two reactants, where the product is a polymer containing a single repeating structural motif, the product obtained will consist of a statistical mixture of a large number of individual molecules each having differing lengths and molecular weights.
In spite of these limitations, those skilled in the art have developed strategies by which these methods can be exploited. Average chain length can be controlled roughly by the ratio of initiator to monomer, or by quenching with an additive giving a range of molecular weights. Macroscopic properties can be modulated by the addition of comonomers which are incorporated randomly into the backbone. However, these methods possess no ability to have discreet or even reproducible microsequence control, and the "address" of a singular functionality added to the polymerization reaction is statistically determined.
Most natural biological polymers, such as oligonucleotides, proteins and polysaccharides, on the other hand, contain precise sequences of monomer units which confer the polymer with highly specific functional properties, including a specific three dimensional structure. Recent advances in the understanding of the complex mechanisms of biochemical processes and of the underlying structure-function relationships of biological polymers involved in the replication (DNA--DNA), storage (DNA), transcription (DNA-RNA), translation (RNA-protein), communication, recognition, control (proteins, peptides, carbohydrates) and function (proteins, oligosaccharides) of all biological systems have illuminated the exquisite sensitivity of these polymers to microsequence variations. A classic example of this is sickle cell anemia which has been shown to be due to a single point mutation in the genetic sequence encoding for the beta chain of hemoglobin. As a result of this mutation, the abnormal hemoglobin contains a single valine in place of a glutamine in the sequence of the protein. This results in an abnormal shape for the hemoglobin, producing the characteristic sickle-shaped cells and the resulting tragic pathological consequences.
The biosynthesis of these biopolymers can be viewed, at a molecular level, to consist of a highly organized series of individual catenation steps, each carried out with specific reactants under highly controlled conditions and mediated by biocalytic agents, principally enzymes. All of the monomers necessary for the construction of these biological polymers are present in the vicinity of the reaction area and are carried by chaperone molecules to the site of their incorporation into the growing chain, where they are released and coupled. Since these polymers were designed by nature to carry out their highly specific functions under physiological conditions (water at pH 7 and physiological temperatures, etc.), and have been programmed by nature to be subject to natural biochemical transformations, such as proteolytic decomposition, they are usually not robust (notable exceptions include structural polymers such as chitin, cotton, skin, silk, hair and other structural materials) and are easily decomposed or denatured by exposure to non-physiological conditions, such as elevated temperatures, organic solvents, extremes of pH, etc. As a result, these molecules are generally ill suited for tasks other than their proper biochemical ones.
Simply put, the makers of polymers, while being able to statistically achieve good and consistent macroscopic properties in the polymeric materials which they produce, have not had any way, up to this point, to control the microscopic make-up of their product. Nature, in producing biomacromolecules, has evolved systems which allow exquisite control over both the microscopic make-up and the macro-structure of its functional polymers. However, these polymers are severely limited in the variety of uses to which they may be applied by their chemical constitution, their lack of stability towards chemical and biochemical agents and their sensitivity to changes in environmental conditions, such as temperature. In addition, the nature of natural scaffolds and substituents and their sensitivity to the chemical conditions necessary to manipulate and to transform them severely limits their utility in producing new materials from these components.